tbuckley/cabot-search huggingface dataset:
Estimated Prevalence and Testing for Albuminuria in US Adults at Risk for Chronic Kidney Disease
Authors: Chi D. Chu, Fang Xia, Yuxian Du, Rakesh Singh, Delphine S. Tuot, Julio A. Lamprea-Montealegre, Ralph Gualtieri, Nick Liao, Sheldon X. Kong, Todd Williamson, Michael G. Shlipak, Michelle M. Estrella
Journal: JAMA Network Open (2023)

Importance Albuminuria testing is crucial for guiding evidence-based treatments to mitigate chronic kidney disease (CKD) progression and cardiovascular morbidity, but it is widely underutilized among persons with or at risk for CKD. Objective To estimate the extent of albuminuria underdetection from lack of testing and evaluate its association with CKD treatment in a large US cohort of patients with hypertension or diabetes. Design, Setting, and Participants This cohort study examined adults with hypertension or diabetes, using data from the 2007 to 2018 National Health and Nutrition Examination Surveys (NHANES) and the Optum deidentified electronic health record (EHR) data set of diverse US health care organizations. Analyses were conducted from October 31, 2022, to May 19, 2023. Main Outcomes and Measures Using NHANES as a nationally representative sample, a logistic regression model was developed to estimate albuminuria (urine albumin-creatinine ratio ≥30 mg/g). This model was then applied to active outpatients in the EHR from January 1, 2017, to December 31, 2018. The prevalence of albuminuria among those with and without albuminuria testing during this period was estimated. A multivariable logistic regression was used to examine associations between having albuminuria testing and CKD therapies within the subsequent year (prescription for angiotensin-converting enzyme inhibitor [ACEi] or angiotensin II receptor blocker [ARB], prescription for sodium-glucose cotransporter 2 inhibitor [SGLT2i], and blood pressure control to less than 130/80 mm Hg or less than 140/90 mm Hg on the latest outpatient measure). Results The total EHR study population included 192 108 patients (mean [SD] age, 60.3 [15.1] years; 185 589 [96.6%] with hypertension; 50 507 [26.2%] with diabetes; mean [SD] eGFR, 84 [21] mL/min/1.73 m 2 ). There were 33 629 patients (17.5%) who had albuminuria testing; of whom 11 525 (34.3%) had albuminuria. Among 158 479 patients who were untested, the estimated albuminuria prevalence rate was 13.4% (n = 21 231). Thus, only 35.2% (11 525 of 32 756) of the projected population with albuminuria had been tested. Albuminuria testing was associated with higher adjusted odds of receiving ACEi or ARB treatment (OR, 2.39 [95% CI, 2.32-2.46]), SGLT2i treatment (OR, 8.22 [95% CI, 7.56-8.94]), and having blood pressure controlled to less than 140/90 mm Hg (OR, 1.20 [95% CI, 1.16-1.23]). Conclusions and Relevance In this cohort study of patients with hypertension or diabetes, it was estimated that approximately two-thirds of patients with albuminuria were undetected due to lack of testing. These results suggest that improving detection of CKD with albuminuria testing represents a substantial opportunity to optimize care delivery for reducing CKD progression and cardiovascular complications.
Association of Wildfire Exposure While Recovering From Lung Cancer Surgery With Overall Survival
Authors: Danlu Zhang, Yuzhi Xi, Daniel J. Boffa, Yang Liu, Leticia M. Nogueira
Journal: JAMA Oncology (2023)

Importance With a changing climate, wildfire activity in the US has increased dramatically, presenting multifaceted and compounding health hazards. Individuals discharged from the hospital following surgical resection of non–small cell lung cancer (NSCLC) are potentially at higher risk from wildfires’ health hazards. Objective To assess the association between wildfire exposure and postoperative long-term overall survival among patients with lung cancer in the US. Design, Setting, and Participants In this cohort study, individuals who underwent curative-intent NSCLC resection between January 1, 2004, and December 31, 2019, were selected from the National Cancer Database. Daily wildfire information was aggregated at the zip code level from the National Aeronautics and Space Administration Fire Information for Resource Management System. The data analysis was performed between July 19, 2022, and April 14, 2023. Exposure An active wildfire detected at the zip code of residence between 0 and 3, 4 and 6, or 7 and 12 months after NSCLC surgery. Main Outcome Overall survival was defined as the interval between age at hospital discharge and age at death, last contact, or study end, whichever came first. Cox proportional hazards were used for estimating hazard ratios (HRs) adjusted for sex, region, metropolitan category, health insurance type, comorbidities, tumor size, lymph node involvement, era, and facility type. Results A total of 466 912 individuals included in the study (249 303 female and [53.4] and 217 609 male [46.6%]; mean [SD] age at diagnosis, 67.3 [9.9] years), with 48 582 (10.4%) first exposed to a wildfire between 0 and 3 months, 48 328 (10.6%) between 4 and 6 months, and 71 735 (15.3%) between 7 and 12 months following NSCLC surgery. Individuals exposed to a wildfire within 3 months (adjusted HR [AHR], 1.43; 95% CI, 1.41-1.45), between 4 and 6 months (AHR, 1.39; 95% CI, 1.37-1.41), and between 7 and 12 months (AHR, 1.17; 95% CI, 1.15-1.19) after discharge from the hospital following stage I to III NSCLC resection had worse overall survival than unexposed individuals. Conclusions In this cohort study, wildfire exposure was associated with worse overall survival following NSCLC surgical resection, suggesting that patients with lung cancer are at greater risk from the health hazards of wildfires and need to be prioritized in climate adaptation efforts.
Biallelic <i>Dicer1</i> Mutations in the Gynecologic Tract of Mice Drive Lineage-Specific Development of <i>DICER1</i> Syndrome–Associated Cancer
Authors: Yemin Wang, Shary Yuting Chen, Monica Ta, Janine Senz, Lan Valerie Tao, Shelby Thornton, Nirupama Tamvada, Winnie Yang, Yana Moscovitz, Eunice Li, Jingjie Guo, Cindy Shen, J. Maxwell Douglas, Amal M. EI-Naggar, Felix K.F. Kommoss, T. Michael Underhill, Naveena Singh, C. Blake Gilks, Gregg B. Morin, David G. Huntsman
Journal: Cancer Research (2023)

DICER1 is an RNase III enzyme essential for miRNA biogenesis through cleaving precursor-miRNA hairpins. Germline loss-of-function DICER1 mutations underline the development of DICER1 syndrome, a rare genetic disorder that predisposes children to cancer development in organs such as lung, gynecologic tract, kidney, and brain. Unlike classical tumor suppressors, the somatic "second hit" in DICER1 syndrome-associated cancers does not fully inactivate DICER1 but impairs its RNase IIIb activity only, suggesting a noncanonical two-hit hypothesis. Here, we developed a genetically engineered conditional compound heterozygous Dicer1 mutant mouse strain that fully recapitulates the biallelic DICER1 mutations in DICER1 syndrome-associated human cancers. Crossing this tool strain with tissue-specific Cre strains that activate Dicer1 mutations in gynecologic tract cells at two distinct developmental stages revealed that embryonic biallelic Dicer1 mutations caused infertility in females by disrupting oviduct and endometrium development and ultimately drove cancer development. These multicystic tubal and intrauterine tumors histologically resembled a subset of DICER1 syndrome-associated human cancers. Molecular analysis uncovered accumulation of additional oncogenic events (e.g., aberrant p53 expression, Kras mutation, and Myc activation) in murine Dicer1 mutant tumors and validated miRNA biogenesis defects in 5P miRNA strand production, of which, loss of let-7 family miRNAs was identified as a putative key player in transcriptomic rewiring and tumor development. Thus, this DICER1 syndrome-associated cancer model recapitulates the biology of human cancer and provides a unique tool for future investigation and therapeutic development.Generation of a Dicer1 mutant mouse model establishes the oncogenicity of missense mutations in the DICER1 RNase IIIb domain and provides a faithful model of DICER1 syndrome-associated cancer for further investigation.
Sex Differences in the Progression and Long-Term Outcomes of Native Mild to Moderate Aortic Stenosis
Authors: Essa H. Hariri, Jessica El Halabi, Nicholas Kassis, Mazen M. Al Hammoud, Osamah Z. Badwan, Habib Layoun, Joseph Kassab, Wael Al Shuab, Agam Bansal, Medhat Farwati, Serge C. Harb, Zoran B. Popović, Lars Svensson, Venu Menon, Samir R. Kapadia
Journal: JACC. Cardiovascular imaging (2023)
pH-responsive polyzwitterion covered nanocarriers for DNA delivery
Authors: Xin Shen, Anjaneyulu Dirisala, Masahiro Toyoda, Yao Xiao, Haochen Guo, Yuto Honda, Takahiro Nomoto, Hiroyasu Takemoto, Yutaka Miura, Nobuhiro Nishiyama
Journal: Journal of Controlled Release (2023)
Dynamic evaluation based on acute-on-chronic liver failure predicts survival of patients after liver transplantation: a cohort study
Authors: Wei Zhang, Pingbo Jin, Junfang Liu, Yue Wu, Rongrong Wang, Yuntao Zhang, Yan Shen, Min Zhang, Xueli Bai, John Fung, Tingbo Liang
Journal: International Journal of Surgery (2023)

Dynamic evaluation of critically ill patients is the key to predicting their outcomes. Most scores based on the Model for End-stage Liver Disease (MELD) and acute-on-chronic liver failure (ACLF) utilize point-in-time assessment. This study mainly aimed to investigate the impact of dynamic clinical course change on post-liver transplantation (LT) survival.This study included 637 adults (overall cohort) with benign end-stage liver diseases. The authors compared the MELD scores and our ACLF-based dynamic evaluation scores. Patients enrolled or transplanted with ACLF-3 were defined as the ACLF-3 cohort ( n =158). The primary outcome was 1-year mortality. ΔMELD and ΔCLIF-OF (Chronic Liver Failure-Organ Failure) represented the respective dynamic changes in liver transplant function. Discrimination was assessed using the area under the curve. A Cox regression analysis identified independent risk factors for specific organ failure and 1-year mortality.Patients were grouped into three groups: the deterioration group (D), the stable group (S), and the improvement group (I). The deterioration group (ΔCLIF-OF ≥2) was more likely to receive national liver allocation ( P =0.012) but experienced longer cold ischemia time ( P =0.006) than other groups. The area under the curves for ΔCLIF-OF were 0.752 for the entire cohort and 0.767 for ACLF-3 cohorts, both superior to ΔMELD ( P <0.001 for both). Compared to the improvement group, the 1-year mortality hazard ratios (HR) of the deterioration group were 12.57 (6.72-23.48) for the overall cohort and 7.00 (3.73-13.09) for the ACLF-3 cohort. Extrahepatic organs subscore change (HR=1.783 (1.266-2.512) for neurologic; 1.653 (1.205-2.269) for circulation; 1.906 (1.324-2.743) for respiration; 1.473 (1.097-1.976) for renal) were key to transplantation outcomes in the ACLF-3 cohort. CLIF-OF at LT (HR=1.193), ΔCLIF-OF (HR=1.354), and cold ischemia time (HR=1.077) were independent risk factors of mortality for the overall cohort, while ΔCLIF-OF (HR=1.384) was the only independent risk factor for the ACLF-3 cohort. Non-ACLF-3 patients showed a higher survival rate than patients with ACLF-3 in all groups ( P =0.002 for I, P =0.005 for S, and P =0.001 for D).This was the first ACLF-based dynamic evaluation study. ΔCLIF-OF was a more powerful predictor of post-LT mortality than ΔMELD. Extrahepatic organ failures were core risk factors for ACLF-3 patients. CLIF-OF at LT, ΔCLIF-OF, and cold ischemia time were independent risk factors for post-LT mortality. Patients with a worse baseline condition and a deteriorating clinical course had the worst prognosis. Dynamic evaluation was important in risk stratification and recipient selection.
Complementary feeding practices are related to the risk of food allergy in the ELFE cohort
Authors: T. Adam, A. Divaret‐Chauveau, C. Roduit, K. Adel‐Patient, A. Deschildre, C. Raherison, M.‐A. Charles, S. Nicklaus, B. de Lauzon‐Guillain
Journal: Allergy (2023)

Abstract Background Conflicting results have been obtained when analyzing the relationship between complementary feeding (CF) practices and allergic diseases in childhood. This study aims to further explore the association between allergic diseases in early childhood ( 10.1016/j.jaci.2012.02.036 ) and the age at CF introduction ( 10.1016/S0140‐6736(15)00149‐X ), food diversity in the first year of life ( 10.1016/j.ijporl.2019.109759 ) and the delayed introduction of major allergenic foods. Methods This analysis focused on 6662 children from the French nationwide ELFE cohort. Data on feeding practices were collected monthly from 3 to 10 months old. Their age at CF introduction was calculated alongside a diversity score, and the number of major allergenic foods (out of eggs, fish, wheat, and dairy products) not introduced at 8 and 10 months. Their associations with parent‐reported allergy‐related health events between 1 and 5.5 years were assessed using logistic regressions adjusted for confounding factors. A sensitivity analysis excluding early allergic cases (occurring between 2 months and 1 or 2 years) was conducted. Results Late CF (&gt;6 months) was related to a higher risk of food allergy (OR [95% CI] = 1.35 [1.02; 1.78]), a low diversity score at 8 months to a higher risk of asthma (OR [95% CI] = 1.22 [1.01; 1.48]), and two allergenic foods or more not being introduced at 10 months to a higher risk of rhinoconjunctivitis (OR [95% CI] = 1.20 [1.00; 1.44]) and food allergy (OR [95% CI] = 2.46 [1.77; 3.42]). Only this last association remained significant after the exclusion of early cases. Conclusion The delayed introduction of major allergenic foods is related to a higher risk of food allergy, which supports the updated guidelines for allergy prevention.
Enzyme‐Responsive Nanoparticles for Dexamethasone Targeted Delivery to Treat Inflammation in Diabetes
Authors: Nathan Schiffmann, Yifei Liang, Carlos E. Nemcovsky, Michal Almogy, Michal Halperin‐Sternfeld, Nathan C. Gianneschi, Lihi Adler‐Abramovich, Eyal Rosen
Journal: Advanced Healthcare Materials (2023)

Abstract Diabetes is a global epidemic accompanied by impaired wound healing and increased risk of persistent infections and resistance to standard treatments. Therefore, there is an immense need to develop novel methods to specifically target therapeutics to affected tissues and improve treatment efficacy. This study aims to use enzyme‐responsive nanoparticles for the targeted delivery of an anti‐inflammatory drug, dexamethasone, to treat inflammation in diabetes. These nanoparticles are assembled from fluorescently‐labeled, dexamethasone‐loaded peptide‐polymer amphiphiles. The nanoparticles are injected in vivo, adjacent to labeled collagen membranes sub‐periosteally implanted on the calvaria of diabetic rats. Following their implantation, collagen membrane resorption is linked to inflammation, especially in hyperglycemic individuals. The nanoparticles show strong and prolonged accumulation in inflamed tissue after undergoing a morphological switch into microscale aggregates. Significantly higher remaining collagen membrane area and less inflammatory cell infiltration are observed in responsive nanoparticles‐treated rats, compared to control groups injected with free dexamethasone and non‐responsive nanoparticles. These factors indicate improved therapeutic efficacy in inflammation reduction. These results demonstrate the potential use of enzyme‐responsive nanoparticles as targeted delivery vehicles for the treatment of diabetic and other inflammatory wounds.
Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Gabriele Todisco, Maria Creignou, Elsa Bernard, Ann-Charlotte Björklund, Pedro Luis Moura, Bianca Tesi, Teresa Mortera-Blanco, Birgitta Sander, Monika Jansson, Gunilla Walldin, Indira Barbosa, Susanne E. Reinsbach, Isabel Juliana Hofman, Christer Nilsson, Tetsuichi Yoshizato, Marios Dimitriou, David Chang, Svannildur Olafsdottir, Sigita Venckute Larsson, Magnus Tobiasson, Luca Malcovati, Petter Woll, Sten Eirik W. Jacobsen, Elli Papaemmanuil, Eva Hellström-Lindberg
Journal: Clinical Cancer Research (2023)

Ring sideroblasts (RS) define the low-risk myelodysplastic neoplasm (MDS) subgroup with RS but may also reflect erythroid dysplasia in higher risk myeloid neoplasm. The benign behavior of MDS with RS (MDSRS+) is limited to SF3B1-mutated cases without additional high-risk genetic events, but one third of MDSRS+ carry no SF3B1 mutation, suggesting that different molecular mechanisms may underlie RS formation. We integrated genomic and transcriptomic analyses to evaluate whether transcriptome profiles may improve current risk stratification.
SLN124, a GalNAc conjugated 19‐mer siRNA targeting <i>tmprss6</i>, reduces plasma iron and increases hepcidin levels of healthy volunteers
Authors: John B. Porter, Alison Scrimgeour, Alberto Martinez, Leo James, Manuela Aleku, Rosamund Wilson, Martina Muckenthaler, Malcolm Boyce, Denise Wilkes, Ute Schaeper, Giles V. Campion
Journal: American Journal of Hematology (2023)

Abstract SLN124, an N‐acetylgalactosamine conjugated 19‐mer short interfering RNA, is being developed to treat iron‐loading anemias (including beta‐thalassemia and myelodysplastic syndromes) and myeloproliferative neoplasms (polycythemia vera). Through hepatic targeting and silencing of the TMPRSS6 gene, SLN124 increases endogenous hepcidin synthesis. This is the first clinical report of an siRNA targeting a component of iron homeostasis. This first‐in‐human, phase 1 study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of SLN124 (1.0, 3.0, and 4.5 mg/kg) in healthy volunteers. Twenty‐four participants were randomized in three sequential cohorts of eight subjects, each to receive a single dose of either SLN124 or placebo (6:2 randomization), administered subcutaneously. There were no serious or severe adverse events, or discontinuations due to adverse events, and most treatment‐emergent adverse events were mild, including transient mild injection site reactions, resolving without intervention. SLN124 was rapidly absorbed, with a median t max of 4–5 h across all treatment groups, and largely eliminated from plasma by 48 h. Plasma concentrations increased in a greater than dose proportional fashion between treatment groups. In all SLN124 groups, a dose‐related effect was observed across iron metabolism markers, and across erythroid markers, SLN124 resulted in increased plasma hepcidin levels, peaking around Day 29, and consequent dose‐related sustained reductions in plasma iron and transferrin saturation with decreased reticulocyte production, MCHC, and MCV. Results suggest duration of action lasting up to 56 days after a single SLN124 dose, on hepcidin and hematological parameters of iron metabolism (serum iron and TSAT).
Examination of HIV Preexposure Prophylaxis Need, Availability, and Potential Pharmacy Integration in the Southeastern US
Authors: Kristin R. V. Harrington, Christina Chandra, Daniel I. Alohan, Diego Cruz, Henry N. Young, Aaron J. Siegler, Natalie D. Crawford
Journal: JAMA Network Open (2023)

Daily preexposure prophylaxis (PrEP) use can prevent up to 99% of HIV infections; however, PrEP uptake is low due to poor access to PrEP-prescribing locations for populations at increased risk for HIV, especially in the southeastern US. Pharmacies are a feasible option to increase PrEP access, but little is known about how they could complement current PrEP-prescribing locations.To examine geographic distributions of current PrEP-prescribing locations compared with pharmacies and the facility to need ratios (PFNRs) according to HIV risk in the Southeast and describe the potential reach of pharmacies to expand PrEP access.Data for this cross-sectional study of PrEP-prescribing locations and pharmacies were compiled from January 1 to December 31, 2021. States or specific counties in the Southeast included in this study were jurisdictions identified as high-priority areas for the Ending the HIV Epidemic in the US (EHE) initiative.Expansion of HIV prevention services to pharmacies.Choropleth maps of 5-year HIV risk per 100 000 persons were developed for EHE jurisdictions in the southeastern US. PrEP-prescribing locations (obtained from a national database of PrEP prescribers) and pharmacies (obtained from state pharmacy boards) were overlayed on HIV risk maps. The PFNRs by state were calculated as number of facilities (PrEP-prescribing locations or pharmacies) divided by 5-year HIV risk per 100 000 persons. Lower PFNRs indicated lower geographic availability of locations to meet the needs of the population at risk for HIV. The PFNRs for current PrEP-prescribing locations vs pharmacies were compared.Among the 2 southeastern states and 13 counties in 4 southeastern states included, PrEP-prescribing locations were unequally distributed across EHE areas, with substantially fewer in areas at high risk for HIV. Pharmacies were evenly dispersed across areas regardless of HIV risk. The mean PFNR across all states for current PrEP-prescribing locations was 0.008 (median, 0.000 [IQR, 0.000-0.003]); for pharmacies, it was 0.7 (median, 0.3 [IQR, 0.01-0.1]). The PFNRs were at least 20.3 times higher for pharmacies compared with PrEP-prescribing locations. States with the greatest potential increase in PFNRs with expansion to pharmacies included Kentucky, South Carolina, and Tennessee.The findings of this cross-sectional study suggest that expanding HIV prevention services to pharmacies in EHE areas in the Southeast could significantly increase capacity to reach individuals at increased risk of HIV transmission. Legislation aimed at allowing pharmacists to prescribe PrEP and provide HIV prevention services may be an important next step in ending the HIV epidemic.
Managing raised ferritin in primary care
Authors: Stuart Stewart, William Evans, Iain Turnbull, Charlotte Bradbury, Judith Hayward, Jeremy Shearman
Journal: BMJ (2023)

What you need to know• Raised levels of ferritin can be associated with several serious underlying conditions and should be investigated appropriately • Determine whether raised ferritin reflects iron overload or another disease process • Initial tests for investigating raised ferritin in primary care are fasting transferrin saturation, full blood count, liver blood tests, and C reactive protein
Sunsets
Authors: Brian R. Smith
Journal: JAMA Oncology (2023)

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